Distal trisomy 14 (q24 --> qter) and aorto-pulmonary window: a case report and review of the literature.

A newborn female with partial trisomy for the distal part of the long arm of the chromosome 14 (14q24 --> qter) resulting from a paternal balanced translocation (3;14) is described. We compare her phenotype with eight other individuals with trisomy 14q24 --> qter.

Prevalence and factors associated with difficulty and intention to quit smoking in Switzerland.

ABSTRACT: BACKGROUND: Recent data indicate a slight decrease in the prevalence of smoking in Switzerland, but little is known regarding the intention and difficulty to quit smoking among current smokers. Hence, we aimed to quantify the difficulty and intention to quit smoking among current smokers in Switzerland. METHODS: Cross-sectional study including 607 female and 658 male smokers. Difficulty, intention and motivation to quit smoking were assessed by questionnaire. RESULTS: 90% of women and 85% of men reported being "very difficult" or "difficult" to quit smoking. Almost three quarters of smokers (73% of women and 71% of men) intended to quit; however, less than 20% of them were in the preparation stage and 40% were in the precontemplation stage. On multivariate analysis, difficulty to quit was lower among men (Odds ratio and 95% [confidence interval]: 0.51 [0.35-0.74]) and increased with nicotine dependence and number of previous quitting attempts (OR=3.14 [1.75-5.63] for 6+ attempts compared to none). Intention to quit decreased with increasing age (OR=0.48 [0.30-0.75] for [greater than or equal to]65 years compared to <45 years) and increased with nicotine dependence, the number of previous quitting attempts (OR=4.35 [2.76-6.83] for 6+ attempts compared to none) and among non-cigarette smokers (OR=0.51 [0.28-0.92]). Motivation to quit was inversely associated with nicotine dependence and positively associated with the number of previous quitting attempts and personal history of lung disease. CONCLUSION: Over two thirds of Swiss smokers want to quit. However, only a small fraction wishes to do so in the short term. Nicotine dependence, previous attempts to quit or previous history of lung disease are independently associated with difficulty and intention to quit.

Increasing respiratory dead space improves sleep disordered breathing and hypoxemia in patients with chronic mountain sickness

Background: Chronic mountain sickness (CMS), which is characterised by hypoxemia, erythrocytosis and pulmonary hypertension, is a major public health problem in high-altitude dwellers. The only existing treatment is descent to low altitude, an option that for social reasons almost never exists. Sleep disordered breathing may represent an underlying mechanism. We recently found that in mountaineers increasing the respiratory dead space markedly improves sleep disordered breathing. The aim of the present study was to assess the effects of this procedure on sleep disordered breathing in patients with CMS. Methods: In 10 male Bolivian high-altitude dwellers (mean ± SD age, 59 ± 9 y) suffering from CMS (haemoglobin >20 g/L) full night sleep recordings (Embletta, RespMed) were obtained in La Paz (3600 m). In random order, one night was spent with a 500 ml increase in dead space through a custom designed full face mask and the other night without it. Exclusion criteria were: secondary erythrocytosis, smoking, drug intake, acute infection, cardio- pulmonary or neurologic disease and travelling to low altitude in the preceding 6 months. Results: The major new finding was that added dead space dramatically improved sleep disordered breathing in patients suffering from CMS. The apnea/hypopnea index decreased by >50% (from 34.5 ± 25.0 to 16.8 ± 14.9, P = 0.003), the oxygen desaturation index decreased from 46.2 ± 23.0 to 27.2 ± 20.0 (P = 0.0004) and hypopnea index from 28.8 ± 20.9 to 16.3 ± 14.0 (P = 0.01), whereas nocturnal oxygen saturation increased from 79.8 ± 3.6 to 80.9 ± 3.0% (P = 0.009). The procedure was easily accepted and well tolerated. Conclusion: Here, we show for the very first time that an increase in respiratory dead space through a fitted mask dramatically improves nocturnal breathing in high-altitude dwellers suffering from CMS. We speculate that when used in the long-term, this procedure will improve erythrocytosis and pulmonary hypertension and offer an inexpensive and easily implementable treatment for this major public health problem.

High altitude journeys and flights are associated with the increased risk of flares in IBD patients

Background: There is increasing evidence that hypoxia induces inflammation in the gastrointestinal tract. The clinical impact of hypoxia in patients with inflammatory bowel disease (IBD) is so far poorly investigated. Aim: We wanted to evaluate if flights and journeys to regions >= 2000 meter above sea level are associated with the occurrence of flares in IBD patients in the following 4 weeks. Methods: A questionnaire was completed by inpatients and outpatients of the IBD clinics of three tertiary referral centers presenting with an IBD flare. Patients were inquired about their habits in the 4 weeks prior to the flare. Patients with flares were matched with an IBD group in remission during the observation period (according to age, gender, smoking habits, and medication). Results: A total of 103 IBD patients were included (43 Crohn's disease (CD), whereof 65% female, 60 ulcerative colitis, whereof 47% female, mean age 39.3 ± 14.6 years for CD and 43.1 ± 14.2 years for UC). Fifty-two patients with flares were matched to 51 patients without flare. Overall, IBD-patients with flares had significantly more frequently a flight and/or journey to regions >= 2000 meters above sea level in the observation period compared to the patients in remission (21/52 (40.4%) vs. 8/51 (15.7%), p = 0.005). There was a statistically significant correlation between the occurrence of a flare and a flight and/or journey to regions >= 2000 meters above sea level among CD patients with flares as compared to CD patients in remission (8/21 (38.1%) vs. 2/22 (9.1%), p = 0.024). A trend for more frequent flights and high-altitude journeys was observed in UC patients with flares (13/31 (41.9%) vs. 6/29 (20.7%), p = 0.077). Mean flight duration was 5.8 ± 4.3 hours. The groups were controlled for the following factors (always flare group cited first): age (39.6 ± 13.4 vs. 43.5 ± 14.6, p = 0.102), smoking (16/52 vs. 10/51, p = 0.120), regular sports activities (32/52 vs. 33/51, p = 0.739), treatment with antibiotics in the 4 weeks before flare (8/52 vs. 7/51, p = 0.811), NSAID intake (12/52 vs. 7/51, p = 0.221), frequency of chronic obstructive pulmonary disease (both groups 0) and oxygen therapy (both groups 0). Conclusion: IBD patients with a flare had significantly more frequent flights and/or high-altitude journeys within four weeks prior to the IBD flare compared to the group that was in remission. We conclude that flights and stays in high altitude are a risk factor for IBD flares.

Predicting smoking cessation and its relapse in HIV-infected patients: the Swiss HIV Cohort Study.

OBJECTIVES: The aim of the study was to assess whether prospective follow-up data within the Swiss HIV Cohort Study can be used to predict patients who stop smoking; or among smokers who stop, those who start smoking again. METHODS: We built prediction models first using clinical reasoning ('clinical models') and then by selecting from numerous candidate predictors using advanced statistical methods ('statistical models'). Our clinical models were based on literature that suggests that motivation drives smoking cessation, while dependence drives relapse in those attempting to stop. Our statistical models were based on automatic variable selection using additive logistic regression with component-wise gradient boosting. RESULTS: Of 4833 smokers, 26% stopped smoking, at least temporarily; because among those who stopped, 48% started smoking again. The predictive performance of our clinical and statistical models was modest. A basic clinical model for cessation, with patients classified into three motivational groups, was nearly as discriminatory as a constrained statistical model with just the most important predictors (the ratio of nonsmoking visits to total visits, alcohol or drug dependence, psychiatric comorbidities, recent hospitalization and age). A basic clinical model for relapse, based on the maximum number of cigarettes per day prior to stopping, was not as discriminatory as a constrained statistical model with just the ratio of nonsmoking visits to total visits. CONCLUSIONS: Predicting smoking cessation and relapse is difficult, so that simple models are nearly as discriminatory as complex ones. Patients with a history of attempting to stop and those known to have stopped recently are the best candidates for an intervention.

Evaluation des modifications anatomiques et fonctionnelles de la macula après chirurgie des membranes néovasculaires rétrofovéolaires dans la dégénérescence maculaire liée à l'âge [Evaluation of functional and anatomical changes in the macula after surgery for retro-foveal neovascularization of membranes in age-related macular degeneration].

PURPOSE: The aim of this study was to evaluate the direct effect of surgical treatment of subfoveolar neovascular membranes in age related macular degeneration to macular functions. PATIENTS AND METHODS: Thirteen eyes of 13 patients were included in this study. Macular function was assayed by visual acuity and central visual field using the Octopus perimeter before surgery and in the first three post operative months. Pre and post operative fluorescein angiography frames were digitalized and the size of each lesions were compared. RESULTS: After a 3 months follow up, visual acuity remained stable or improved in 66% of the patients. However, visual acuity was better than 0.1 in 15% of the patients. Central visual field comparison disclosed a significant worsening of the retinal sensitivity in the 3 degree field surrounding the central point. On fluorescein frames, submacular scar was 141% of the size of the neovascular membrane. After a mean follow up of 6.9 months (range 3-14), one case of recurrence occurred. A cataract was observed in 85% of the phakic patients followed for more than six months. CONCLUSION: After a short term follow up, surgery can stabilise visual acuity, even though it remains poor. A worsening of the scotoma in the 3 degrees surrounding the central point is observed. However, patients noticed a subjective visual improvement in 62% of the case.

Anterior ischemic optic neuropathy in eyes with optic disc drusen.

BACKGROUND: There have been anecdotal reports of anterior ischemic optic neuropathy (AION) occurring in eyes with optic disc drusen (ODD), but the clinical features of this condition have not been well characterized. OBJECTIVES: To better describe the clinical features of AION associated with ODD and to compare the clinical features of this condition with those of "garden variety" nonarteritic AION. METHODS: We reviewed the medical records of 20 patients who experienced an episode of AION in an eye with ODD. In 4 patients, both eyes were affected; thus, 24 eyes were studied. The diagnosis of ODD was made by ophthalmoscopic identification, orbital ultrasonography, or computed tomographic scanning. We recorded age, sex, vascular risk factors, symptoms, visual acuity, visual fields, and results of the follow-up examination in all patients. These findings were compared with data from previously reported series of patients with nonarteritic AION. RESULTS: Our 20 patients included 14 men and 6 women (age range, 18-69 years; mean, 49.4 years). Vascular risk factors were identified in 10 patients (50%). Three patients reported episodes of transient visual loss before their fixed deficit. The visual acuity at the initial examination was 20/60 or better in 15 (62%) of the 24 eyes; 8 had a visual acuity of 20/20. The predominant pattern of visual field loss was an altitudinal or arcuate defect in 19 (79%) and a centrocecal scotoma in 5 (21%) of the 24 eyes. There was subjective worsening of vision before the initial neuro-ophthalmic examination in 11 eyes (46%) and objective documentation of progression in 7 eyes (29%). The final visual acuity was 20/40 or better in 13 (62%) of 21 eyes and 20/200 or worse in 3 (14%) of 21 eyes. CONCLUSIONS: Our patients were strikingly similar to those with nonarteritic AION unassociated with drusen in regard to prevalence of vascular risk factors, pattern of visual field loss, and occurrence of a subsequent similar event in the fellow eye. In contrast, however, patients with ODD-AION were younger than those with nonarteritic AION, were more likely to report preceding episodes of transient visual obscuration, and enjoyed a more favorable visual outcome.

Inflammatory Markers and Incident Heart Failure Risk in Older Adults: The Health, Aging, and Body Composition Study

Background: Inflammation is associated with heart failure (HF) risk factors and also directly affects myocardial function. However, the association between inflammation and HF risk in older adults has not been adequately evaluated. Methods: The association of baseline serum concentrations of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF- ), and C-reactive protein (CRP) with incident HF was assessed with Cox proportional hazards models among 2610 older persons without prevalent HF enrolled in the Health, Aging, and Body Composition (Health ABC) Study (age, 73.6±2.9 years; 48.3% men; 59.6% white). Results: Median (interquartile range) baseline concentrations of IL-6, TNF- , and CRP were 1.80 (1.23, 2.76) pg/mL, 3.14 (2.41, 4.06) pg/mL, and 1.64 (0.99, 3.04) µg/mL, respectively. On follow-up (median, 9.4 years), 311 participants (11.9%) developed HF. In models controlling for clinical predictors of HF and incident coronary heart disease, doubling of IL-6, TNF- , and CRP concentrations was associated with 34% (95% CI, 18 -52%; P<.001), 33% (95% CI, 9 - 63%; P=.006), and 13% (95% CI, 3-24%; P=.01) increase in HF risk, respectively. In models including all 3 markers, IL-6 and TNF- , but not CRP, remained significant. Findings were similar across sex and race. Post-HF ejection fraction (EF) was available in 239 (76.8%) cases. When only cases with preserved EF were considered (n=105), IL-6 (HR per doubling, 1.57; 95% CI, 1.28 -1.94; P<.001), TNF- (HR per doubling, 1.59; 95% CI, 1.12-2.26; P=.01), and CRP (HR per doubling, 1.23; 95% CI, 1.05-1.44; P=.01) were all associated with HF risk in adjusted models. In contrast, when only cases with reduced EF (n=134) were considered, only IL-6 attained marginal significance in adjusted models (HR per doubling, 1.20; 95% CI, 0.99 -1.46; P=.06). Participants with 2 or 3 markers above median had pronounced HF risk in adjusted models (HR, 1.66; 95% CI, 1.12-2.46; P=.01; and HR, 1.76; 95% CI, 1.16 -2.65; P=.007, respectively). Addition of IL-6 to the clinical Health ABC HF model improved discrimination (C index from 0.717 to 0.734; P=.001) and fit (decreased Bayes information criterion by 17.8; P<.001). Conclusions: Inflammatory markers are associated with HF risk among older adults and may improve HF risk stratification.

Prevalence and factors associated with difficulty and intention to quit smoking in Switzerland.

BACKGROUND: Recent data indicate a slight decrease in the prevalence of smoking in Switzerland, but little is known regarding the intention and difficulty to quit smoking among current smokers. Hence, we aimed to quantify the difficulty and intention to quit smoking among current smokers in Switzerland. METHODS: Cross-sectional study including 607 female and 658 male smokers. Difficulty, intention and motivation to quit smoking were assessed by questionnaire. RESULTS: 90% of women and 85% of men reported being "very difficult" or "difficult" to quit smoking. Almost three quarters of smokers (73% of women and 71% of men) intended to quit; however, less than 20% of them were in the preparation stage and 40% were in the precontemplation stage. On multivariate analysis, difficulty to quit was lower among men (Odds ratio and 95% [confidence interval]: 0.51 [0.35-0.74]) and increased with nicotine dependence and number of previous quitting attempts (OR=3.14 [1.75-5.63] for 6+ attempts compared to none). Intention to quit decreased with increasing age (OR=0.48 [0.30-0.75] for ≥65 years compared to <45 years) and increased with nicotine dependence, the number of previous quitting attempts (OR=4.35 [2.76-6.83] for 6+ attempts compared to none) and among non-cigarette smokers (OR=0.51 [0.28-0.92]). Motivation to quit was inversely associated with nicotine dependence and positively associated with the number of previous quitting attempts and personal history of lung disease. CONCLUSION: Over two thirds of Swiss smokers want to quit. However, only a small fraction wishes to do so in the short term. Nicotine dependence, previous attempts to quit or previous history of lung disease are independently associated with difficulty and intention to quit.

Severe traumatic brain injury in a high-income country: an epidemiological study.

This adult cohort determined the incidence and patients' short-term outcomes of severe traumatic brain injury (sTBI) in Switzerland and age-related differences. A prospective cohort study with a follow-up at 14 days was performed. Patients ≥16 years of age sustaining sTBI and admitted to 1 of 11 trauma centers were included. sTBI was defined by an Abbreviated Injury Scale of the head (HAIS) score >3. The centers participated from 6 months to 3 years. The results are presented as percentages, medians, and interquartile ranges (IQRs). Subgroup analyses were performed for patients ≤65 years (younger) and >65 (elderly). sTBI was observed in 921 patients (median age, 55 years; IQR, 33-71); 683 (74.2%) were male. Females were older (median age, 67 years; IQR, 42-80) than males (52; IQR, 31-67; p<0.00001). The estimated incidence was 10.58 per 100,000 inhabitants per year. Blunt trauma was observed in 879 patients (95.4%) and multiple trauma in 283 (30.7%). Median Glasgow Coma Score (GCS) on the scene was 9 (IQR 4-14; 8 in younger, 12 in elderly) and in emergency departments 5 (IQR, 3-14; 3 in younger, 8 in elderly). Trauma mechanisms included the following: 484 patients with falls (52.6%; younger, 242 patients [50.0%]; elderly, 242 [50.0%]), 291 with road traffic accidents (31.6%; younger, 237 patients [81.4%]; elderly, 54 [18.6%]), and 146 with others (15.8%). Mortality was 30.2% (24.5% in younger, 40.9% in elderly). Median GCS at 14 days was 15 (IQR, 14-15) without differences among subgroups. Estimated incidence of sTBI in Switzerland was low, age was high, and mortality considerable. The elderly had higher initial GCS and a higher death rate, but high GCS at 14 days.

Greenstick fractures of the middle third of the forearm. A prospective multi-centre study.

BACKGROUND: Greenstick fractures suffered during growth have a high risk for refracture and posttraumatic deformity, particularly at the forearm diaphysis. The use of a preemptive completion of the fracture by manipulation of the concave cortex is controversial and data supporting this approach are few. AIM: Aim of this study was to determine the factors which predispose to refracture and deformities, and to define therapeutic strategies. METHODS: We prospectively gathered clinical and radiographic data over a period of one year on greenstick fractures of the middle third of the forearm in children as part of a multi-centre study. Endpoint was a follow-up visit at one year. Radiographic deformity, state of consolidation at resumption of physical activities and refracture rate were analysed statistically (ANOVA, Student's t-test and Pearson's chi-square test) with regard to patient age, gender, fracture type, therapy and time in plaster. RESULTS: We collected the data of 103 patients (63 boys, 40 girls), average age 6.6 years (1.3-14.5 years), the vast majority of whom had a combined greenstick fracture of the radius and ulna. 6.7% of the patients sustained a refracture within 49 days (29-76) after plaster removal. They were significantly older (p=0.017) with a significantly higher incidence of manual completion of the fracture with radiographic signs of partial consolidation (p=0.025). Residual deformities were significantly smaller after completion of the fracture compared to reduction without completion (p=0.019) or plaster fixation alone (p<0.005). CONCLUSIONS: Completion of a greenstick fracture does not prevent refracture. Nevertheless, it diminishes the extent of secondary deformities in cases where the primary angulation exceeds the remodelling capacity. Prevention of refracture should include a routine radiographic follow-up 4-6 weeks after injury with continuation of plaster fixation in cases of partial consolidation.

High altitude journeys and flights are associated with an increased risk of flares in inflammatory bowel disease patients.

BACKGROUND AND AIMS: Hypoxia can induce inflammation in the gastrointestinal tract. However, the impact of hypoxia on the course of inflammatory bowel disease (IBD) is poorly understood. We aimed to evaluate whether flights and/or journeys to regions lying at an altitude of >2000 m above the sea level are associated with flare-ups within 4 weeks of the trip. METHODS: IBD patients with at least one flare-up during a 12-month observation period were compared to a group of patients in remission. Both groups completed a questionnaire. RESULTS: A total of 103 IBD patients were included (43 with Crohn's disease (CD): mean age 39.3 ± 14.6 years; 60 with ulcerative colitis (UC): mean age 40.4 ± 15.1 years). Fifty-two patients with flare-ups were matched to 51 patients in remission. IBD patients experiencing flare-ups had more frequently undertaken flights and/or journeys to regions >2000 m above sea level within four weeks of the flare-up when compared to patients in remission (21/52 [40.4%] vs. 8/51 [15.7%], p=0.005). CONCLUSIONS: Journeys to high altitude regions and/or flights are a risk factor for IBD flare-ups occurring within 4 weeks of travel.

Tandem repeat sequence variation as causative cis-eQTLs for protein-coding gene expression variation: the case of CSTB.

Association studies have revealed expression quantitative trait loci (eQTLs) for a large number of genes. However, the causative variants that regulate gene expression levels are generally unknown. We hypothesized that copy-number variation of sequence repeats contribute to the expression variation of some genes. Our laboratory has previously identified that the rare expansion of a repeat c.-174CGGGGCGGGGCG in the promoter region of the CSTB gene causes a silencing of the gene, resulting in progressive myoclonus epilepsy. Here, we genotyped the repeat length and quantified CSTB expression by quantitative real-time polymerase chain reaction in 173 lymphoblastoid cell lines (LCLs) and fibroblast samples from the GenCord collection. The majority of alleles contain either two or three copies of this repeat. Independent analysis revealed that the c.-174CGGGGCGGGGCG repeat length is strongly associated with CSTB expression (P = 3.14 × 10(-11)) in LCLs only. Examination of both genotyped and imputed single-nucleotide polymorphisms (SNPs) within 2 Mb of CSTB revealed that the dodecamer repeat represents the strongest cis-eQTL for CSTB in LCLs. We conclude that the common two or three copy variation is likely the causative cis-eQTL for CSTB expression variation. More broadly, we propose that polymorphic tandem repeats may represent the causative variation of a fraction of cis-eQTLs in the genome.

Trends in the association between height and socioeconomic indicators in France, 1970-2003

Average physical stature has increased dramatically during the 20th century in many populations across the world with few exceptions. It remains unclear if social inequalities in height persist despite improvements in living standards in the welfare economies of Western Europe. We examined trends in the association between height and socioeconomic indicators in adults over three decades in France. The data were drawn from the French Decennial Health Surveys: a multistage, stratified, random survey of households, representative of the population, conducted in 1970, 1980, 1991, and 2003. We categorised age into 10-year bands, 25-34, 35-44, 45-54 and 55-64 years. Education and income were the two socioeconomic measures used. The slope index of inequality (SII) was used as a summary index of absolute social inequalities in height. The results show that average height increased over this period; men and women aged 25-34 years were 171.9 and 161.2 cm tall in 1970 and 177.0 and 164.0 cm in 2003, respectively. However, education-related inequalities in height remained unchanged over this period and in men were 4.48 cm (1970), 4.71 cm (1980), 5.58 cm (1991) and 4.69 cm (2003), the corresponding figures in women were 2.41, 2.37, 3.14 and 2.96 cm. Income-related inequalities in height were smaller and much attenuated after adjustment for education. These results suggest that in France, social inequalities in adult height in absolute terms have remained unchanged across the three decades under examination.